HIV-1 RNA levels and antiretroviral drug resistance in blood and non-blood compartments from HIV-1-infected men and women enrolled in AIDS clinical trials group study A5077.

TitleHIV-1 RNA levels and antiretroviral drug resistance in blood and non-blood compartments from HIV-1-infected men and women enrolled in AIDS clinical trials group study A5077.
Publication TypeJournal Article
Year of Publication2014
AuthorsKantor R, Bettendorf D, Bosch RJ, Mann M, Katzenstein D, Cu-Uvin S, D'Aquila R, Frenkel L, Fiscus S, Coombs R
Corporate AuthorsACTG A5077 Study Team
JournalPLoS One
Volume9
Issue4
Paginatione93537
Date Published2014
ISSN1932-6203
KeywordsAcquired Immunodeficiency Syndrome, Adult, Anti-HIV Agents, Blood, Body Fluid Compartments, Drug Resistance, Viral, Female, Genotype, HIV Infections, HIV-1, Humans, Longitudinal Studies, Male, Middle Aged, RNA, Viral, Saliva, Viral Load, Virus Shedding
Abstract

BACKGROUND: Detectable HIV-1 in body compartments can lead to transmission and antiretroviral resistance. Although sex differences in viral shedding have been demonstrated, mechanisms and magnitude are unclear. We compared RNA levels in blood, genital-secretions and saliva; and drug resistance in plasma and genital-secretions of men and women starting/changing antiretroviral therapy (ART) in the AIDS Clinical Trials Group (ACTG) 5077 study.

METHODS: Blood, saliva and genital-secretions (compartment fluids) were collected from HIV-infected adults (≥ 13 years) at 14 United-States sites, who were initiating or changing ART with plasma viral load (VL) ≥ 2,000 copies/mL. VL testing was performed on all compartment fluids and HIV resistance genotyping on plasma and genital-secretions. Spearman rank correlations were used to evaluate concordance and Fisher's and McNemar's exact tests to compare VL between sexes and among compartments.

RESULTS: Samples were available for 143 subjects; 36% treated (23 men, 29 women) and 64% 'untreated' (40 men, 51 women). RNA detection was significantly more frequent in plasma (100%) than genital-secretions (57%) and saliva (64%) (P<0.001). A higher proportion of men had genital shedding versus women (78% versus 41%), and RNA detection was more frequent in saliva versus genital-secretions in women when adjusted for censoring at the limit of assay detection. Inter-compartment fluid VL concordance was low in both sexes. In 22 (13 men, 9 women) paired plasma-genital-secretion genotypes from treated subjects, most had detectable resistance in both plasma (77%) and genital-secretions (68%). Resistance discordance was observed between compartments in 14% of subjects.

CONCLUSIONS: HIV shedding and drug resistance detection prior to initiation/change of ART in ACTG 5077 subjects differed among tissues and between sexes, making the gold standard blood-plasma compartment assessment not fully representative of HIV at other tissue sites. Mechanisms of potential sex-dependent tissue compartmentalization should be further characterized to aid in optimizing treatment and prevention of HIV transmission.

TRIAL REGISTRATION: ClinicalTrials.gov NCT00007488.

DOI10.1371/journal.pone.0093537
Alternate JournalPLoS ONE
PubMed ID24699474
PubMed Central IDPMC3974754
Grant ListAI- 27664 / AI / NIAID NIH HHS / United States
AI-27757 / AI / NIAID NIH HHS / United States
AI-38855 / AI / NIAID NIH HHS / United States
AI-38858 / AI / NIAID NIH HHS / United States
AI-50410 / AI / NIAID NIH HHS / United States
AI-68634 / AI / NIAID NIH HHS / United States
AI-68636 / AI / NIAID NIH HHS / United States
HD-40540 / HD / NICHD NIH HHS / United States
P01 HD040540 / HD / NICHD NIH HHS / United States
P30 AI027757 / AI / NIAID NIH HHS / United States
U01 AI038855 / AI / NIAID NIH HHS / United States
U01 AI038858 / AI / NIAID NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States
UM1 AI068632 / AI / NIAID NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States
UM1 AI069412 / AI / NIAID NIH HHS / United States
UM1 AI106701 / AI / NIAID NIH HHS / United States